Биологические науки /6. Микробиология

A. S. Gotsulya, prof. Ye. G. Knysh, O. O. Mikolasyuk, J. R. Gladskaya, O. M. Achkasova

Zaporizhzhya State Medical University, Ukraine

Research of the antimicrobial activity of 2-[4-(2-methoxy-phenyl)-5-R-4Н-1,2,4-triazole-3-ylthio]acetic acid salts

During the last decades, open and synthesized thousands of antimicrobial drugs with different spectra of biological action. However, only their limited number finds a practical application. This is explained by the fact that the majority of antimicrobial drugs do not meet the requirements of practical medicine. Some of them possess a high toxicity, and some are carcinogenic agents.

The resistance to antimicrobial preparations determines natural (internal) and acquired factors. Nature and mechanisms of the resistance of pathogenic for organism bacteria are well studied. Therefore, nowadays, the main way of the resistance overcoming to chemotherapeutic agents is the synthesis and application of new antimicrobial drugs.

Synthesis of the chemical compounds and their introduction in a state of antimicrobial methods will increase the quality of preventive and medicinal measures in cattle- breading.

The appearance of resistant strains of microorganisms to antibiotics is making necessary thorough searching of the substances which are safe to the animals and at the same time are lethal for such microorganisms.

Antimicrobial activity was studied in experiments in vitro by "serial dilution" method on liquid nutrient medium.

As culture medium used aminopeptyde, previously diluted with water, pH - 7.2.

Microbial load for bacteria - 2,5∙10⁵ cells of 18 hours culture in 1 ml medium. Maximal from the investigated concentrations - 400 mcg/ml.

Antimicrobial activity was evaluated by the method of minimal bacteriostatic concentration of chemical substance in mg/ml. As standards of comparison were used ethacridine lactate and furacilinum.

Identification of antimicrobial activity of the synthesized compounds was conducted on 5 strains: Staphyllococcus aureus 209-P, Escherichia coli 675, Proteus vulgaris 5, Bacillus anthracoides 1312, Pseudomonas aeroginosa 165.

On the antimicrobial activity investigated the salts of 2-[5-R-4-(2- methoxyphenyl)-1,2,4-triazoles-3-ylthio]acetic acids.

As shown by experiments, the most sensitive to studying group of compounds among the examined strains are Bacillus anthracoides 1312. The most active compounds, compared with other, were monoethanolamine 2-[5-phenyl-4-(2-methoxyphenyl)-1,2,4-triazoles-3-ylthio]acetate and ammonium 2-[5-phenyl-4-(2-methoxyphenyl)-1,2,4-triazoles-3-ylthio]acetate. Mild antibacterial effect against the present strains showed sodium 2-[5-phenyl-4-(2-methoxyphenyl)-1,2,4-triazoles-3-yltio]acetate, ammonium 2-[5-methyl-4-(2-methoxyphenyl)-1,2,4-triazoles-3-ylthio]acetate, diethanolammonium 2-[5-methyl-4-(2-methoxyphenyl)-1,2,4-triazoles-3-ylthio]acetate, ammonium 2-[5-phenyl-4-(2-methoxyphenyl)-1,2,4- triazoles-3-ylthio]acetate and diethanolammonium 2-[5-phenyl-4-(2-methoxyphenyl)-1,2,4-triazoles-3-ylthio]acetate.

Ammonium 2-[5-phenyl-4-(2-methoxyphenyl)-1,2,4-triazoles-3-ylthio]acetate also demonstrates one of the lowest indicators of acute toxicity in class (1053 mg/kg). Thus, replacing the ammonium cation in the structure of 2-[5-methyl-4-(2-methoxyphenyl)-1,2,4-triazoles-3-ylthio]acetic acid and 2-[5-phenyl-4-(2-methoxyphenyl)-1,2,4-triazoles-3-ylthio]acetic acid on the sodium cation, potassium, magnesium, monoethanolammonium, tributylammonium, morpholinium or piperidinium leads to loss of antimicrobial activity.

In particular, the replacement of methyl radical into phenyl in position 5 of 1,2,4-triazole cycle of ammonium 2-[5-methyl-4-(2-methoxyphenyl)-1,2,4-triazoles-3-ylthio]acetate leads to the emergence of antimicrobial activity relative to Staphyllococcus aureus and enhancement of activity relative to Bacillus anthracoides. The emergence of antimicrobial activity relative to Bacillus anthracoides also associated with the replacement of the phenyl radical on the methyl by 5-th ring position of 1,2,4-triazoles sodium 2-[5-methyl-4-(2-methoxyphenyl)-1,2,4-triazoles3-ylthio]acetate, monoethanolammonium 2-[5-methyl-4-(2-methoxy-phenyl)-1,2,4-triazoles-3-ylthio]acetate and diethanolammonium 2-[5-methyl-4-(2-methoxyphenyl)-1,2,4-triazoles-3-ylthio]acetate.